Title

TREX-1-Related Disease Associated with the Presence of Cryofibrinogenemia.

Document Type

Article

Publication Date

1-2019

Identifier

DOI: 10.1007/s10875-018-0584-x

Abstract

PURPOSE: Cryofibrinogenemia is a rare cryopathy presenting as acrocyanosis following exposure to cold. Familial presentation has been described but the underlying molecular cause remained undetermined.

METHODS: Forty (40) members from a large family with an initial diagnosis of familial cryofibrinogenemia were interviewed and examined to determine affected status and collect DNA. Exome sequencing was performed on three affected individuals from distinct branches of the pedigree.

RESULTS: Seventeen (17) family members reported a history of acrocyanosis with cold exposure. None reported symptoms were suggestive of lupus. Exome sequencing of three subjects identified the heterozygous mutation D18N in the TREX1 gene which was then confirmed by Sanger sequencing in all affected as well as 2 unaffected family members. The mutation is already being associated with familial chilblain lupus erythematosus (CHLE), and a systematic review of literature was undertaken to compare reports of familial CHLE and cryofibrinogenemia. Both entities were found to share highly similar clinical presentations suggesting they are part of a same syndrome in which cryofibrinogenemia and lupus manifestations have variable penetrance.

CONCLUSIONS: Familial cryofibrinogenemia without lupus should be added to the spectrum of TREX1-related disease.

Journal Title

Journal of clinical immunology

Volume

39

Issue

1

First Page

118

Last Page

125

MeSH Keywords

Adult; Chilblains; Cryoglobulinemia; DNA; Exodeoxyribonucleases; Female; Genetic Predisposition to Disease; Heterozygote; Humans; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; Male; Mutation; Pedigree; Phosphoproteins

Keywords

Acrocyanosis; Auto-inflammation; Auto-inflammatory; Chilblain; Cryofibrinogen; Cryofibrinogenemia; Familial; Genetics; Lupus; TREX1

Library Record

Share

COinS